vtioВестник трансплантологии и искусственных органовRussian Journal of Transplantology and Artificial Organs1995-1191Academician V.I.Shumakov National Medical Research Center of Transplantology and Artificial Organs", Ministry of Health of the Russian Federation10.15825/1995-1191-2023-4-130-138vtio-1718Research ArticleТрансплантомикаTransplantomicsДиагностическая значимость TGF-β1 у реципиентов с дисфункцией трансплантированной почкиDiagnostic significance of TGF-β1 in kidney recipients with graft dysfunctionШевченкоО. П.ShevchenkoО. P.

Moscow

transplant2009@mail.ruШарапченкоС. О.SharapchenkoS. О.

Шарапченко Софья Олеговна

123182, Москва, ул. Щукинская, д. 1

(499) 193-87-62

Sofya Sharapchenko

1, Shchukinskaya str., Moscow, 123182

Phone: (499) 193-87-62

Nyashka1512@yandex.ruВеликийД. А.VelikiyD. A.

Moscow

dim_vel@mail.ruГичкунО. Е.GichkunО. Е.

Moscow

gichkunoe@yandex.ruСтоляревичЕ. С.StolyarevichE. S.

Moscow

stolyarevich@yandex.ruМожейкоН. П.MozheikoN. P.

Moscow

npm_72@mail.ruСайдулаевД. А.SaydulaevD. A.

Moscow

sdzhabrail@yandex.ruКурабековаР. М.KurabekovaR. М.

Moscow

kourabr@yandex.ruВакуроваЕ. А.VakurovaE. A.

Moscow

МамедоваА. А.MamedovaA. A.

Moscow

medicine2494@mail.ruОсобливаяМ. А.OsoblivayaM. A.

Moscow

osoblivaya-91@yandex.ruФГБУ «Национальный медицинский исследовательский центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава России; ФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Минздрава России (Сеченовский Университет)РоссияShumakov National Medical Research Center of Transplantology and Artificial Organs; Sechenov UniversityRussian FederationФГБУ «Национальный медицинский исследовательский центр трансплантологии и искусственных органов имени академика В.И. Шумакова» Минздрава РоссииРоссияShumakov National Medical Research Center of Transplantology and Artificial OrgansRussian FederationФГАОУ ВО Первый Московский государственный медицинский университет имени И.М. Сеченова Минздрава России (Сеченовский университет)Russian FederationSechenov UniversityRussian Federation202314112023254130138Copyright © Шевченко О.П., Шарапченко С.О., Великий Д.А., Гичкун О.Е., Столяревич Е.С., Можейко Н.П., Сайдулаев Д.А., Курабекова Р.М., Вакурова Е.А., Мамедова А.А., Особливая М.А., 20242024Шевченко О.П., Шарапченко С.О., Великий Д.А., Гичкун О.Е., Столяревич Е.С., Можейко Н.П., Сайдулаев Д.А., Курабекова Р.М., Вакурова Е.А., Мамедова А.А., Особливая М.А.Shevchenko О.P., Sharapchenko S.О., Velikiy D.A., Gichkun О.Е., Stolyarevich E.S., Mozheiko N.P., Saydulaev D.A., Kurabekova R.М., Vakurova E.A., Mamedova A.A., Osoblivaya M.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.transpl.ru/vtio/article/view/1718

Разработка методов малоинвазивной диагностики осложнений у реципиентов на основе анализа уровней молекулярных и генетических биомаркеров – актуальная задача современной трансплантологии. К числу потенциальных индикаторов осложнений относится трансформирующий фактор роста бета-1 (TGF-β1), оказывающий множественные эффекты в организме.

Цель

Цель: оценка диагностической значимости TGF-β1, определяемого в сыворотке крови реципиентов, при дисфункции трансплантированной почки.

Материалы и методы

Материалы и методы. В исследование включены 129 реципиентов почки в возрасте от 17 до 68 лет и 35 здоровых лиц. Концентрацию TGF-β1 в сыворотке крови реципиентов определяли иммуноферментным методом.

Результаты

Результаты. В число реципиентов почки вошли 95 пациентов с лабораторными и клиническими признаками дисфункции трансплантата, которым была выполнена биопсия трансплантированной почки с последующим морфологическим исследованием, и 34 реципиента с нормальной функцией. Уровень TGF-β1 у реципиентов почки был достоверно выше, чем у здоровых лиц (p = 0,00001), не коррелировал с большинством параметров анализа крови, со скоростью клубочковой фильтрации (СКФ). У реципиентов почки с дисфункцией трансплантата уровень TGF-β1 значимо выше, чем у остальных реципиентов (р = 0,018). У реципиентов с дисфункцией трансплантата по результатам морфологического исследования выявлены: острый канальцевый некроз (ОКН, n = 11), острое клеточное отторжение (ACR, n = 26), острое гуморальное отторжение (AMR, n = 35), не связанный с иммунным ответом нефросклероз с признаками нефротоксичности ингибиторов кальциневрина (СNI-нефротоксичность, n = 13), возвратный гломерулонефрит (хроническое отторжение трансплантата, n = 10). У реципиентов с повреждениями трансплантата иммунного характера (ACR, AMR и хроническое отторжение) концентрация TGF-β1 в сыворотке крови выше, чем у реципиентов с дисфункцией от иных причин, р < 0,0001. У реципиентов почки с концентрацией TGF-β1 в сыворотке крови, превышающим пороговое значение 94,3 нг/мл, риск выявления дисфункции трансплантата, вызванной иммунными механизмами, выше, чем у остальных реципиентов почки (RR = 2,2 ± 0,22 [95% ДИ 1,46–3,46]), при чувствительности теста 77,5% и специфичности 60,3%.

Заключение

Заключение. Рассчитанный пороговый уровень TGF-β1 в сыворотке крови реципиентов почки может рассматриваться в качестве вспомогательного индикатора дисфункции трансплантата, обусловленной острым или хроническим отторжением.

Development of minimally invasive diagnosis techniques for complications in recipients, based on analysis of the levels of molecular and genetic biomarkers, is an urgent task facing modern transplantology. Transforming growth factor beta 1 (TGF-β1), which has multiple effects in the body, among the potential indicators of complications.

Objective

Objective: to assess the diagnostic significance of serum TGF-β1 in kidney recipients with graft dysfunction.

Materials and methods

Materials and methods. The study included 129 kidney recipients aged 17 to 68 years and 35 healthy subjects. Serum TGF-β1 levels in the recipients were determined by immunoenzyme technique.

Results

Results. Kidney recipients included 95 patients with laboratory and clinical signs of graft dysfunction, who underwent biopsy of the transplanted kidney, followed by morphological examination, and 34 recipients with normal graft function. Serum TGF-β1 levels in the kidney recipients were significantly higher than in their healthy counterparts (p = 0.00001); it did not correlate with most blood test parameters; with the glomerular filtration rate (GFR). Kidney recipients with graft dysfunction had significantly higher TGF-β1 levels than other recipients (p = 0.018). In recipients with graft dysfunction, morphological study revealed the following: acute tubular necrosis (ATN, n = 11), acute T-cell mediated rejection (ACR, n = 26), acute antibody-mediated rejection (AMR, n = 35), non-immune-mediated nephrosclerosis with signs of calcineurin inhibitor nephrotoxicity (CNI nephrotoxicity, n = 13), and recurrent glomerulonephritis (chronic graft rejection, n = 10). Recipients with immune-mediated graft injury (ACR, AMR and chronic rejection) had higher serum TGF-β1 levels than recipients with graft dysfunction resulting from other causes, p < 0.0001. Kidney recipients with serum TGF-β1 levels above the threshold value of 94.3 ng/mL had a higher risk of immune-mediated graft dysfunction than other kidney recipients (RR = 2.2 ± 0.22 [95% CI 1.46–3.46]) with 77.5% test sensitivity and 60.3% specificity.

Conclusion

Conclusion. The calculated threshold serum TGF-β1 level in kidney recipients can be considered as an auxiliary indicator of graft dysfunction resulting from acute or chronic rejection.

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The authors declare that there are no conflicts of interest present.